The program project is composed of three research projects and two core units. The overall goal of these three interlocking and cooperative projects are: a) to develop a better understanding of molecular and immunobiological mehcanisms leading to the production of autoantibodies or autoreactive T cells in individuals or animals with systemic autoimmune diseases. b) To investigate the role of cell mediated immune mechanisms in these diseases. This proposal brings together a group of established investigators from Mount Sinai School of Medicine who have been actively involved in the investigation of autoimmunity. Each project utilizes a unique experimental approach to address disease related questions. The program s strength lies in the use of complementary approaches and different methodologies, which have resulted in productive collaborations between the laboratories involved in this program project during the past ten years to address pertinent and novel questions. This program project will collectively bridge investigators with strong backgrounds and knowledge in pathophysiology from various disciplines: molecular biology, biochemistry, medicine and immunology. This bridging will create a multi-disciplinary approach to basic questions related to the pathogenesis of experimental human systemic autoimmune disease.